Yijie Du

Icariin exerts an antidepressant effect in an unpredictable chronic mild stress model of depression in rats and is associated with the regulation of hippocampal neuroinflammation.

Icariin (ICA), a flavonoid extracted from the traditional Chinese herb Herba Epimedii that can freely cross the blood-brain barrier, inhibits neuroinflammation and attenuates oxidative stress damage. Our previous studies demonstrated that icariin exerts an antidepressant-like activity in a social defeat mouse model. However, it is unknown whether icariin is beneficial for the treatment of depression via its modulation of oxidative stress and neuroinflammation. The objective of this study was to investigate the effects of icariin on the depression-like behaviors in an unpredictable chronic mild stress (CMS) model of depression in rats. Rats exposed to CMS showed behavioral deficits in physical state, the sucrose preference test (SPT) and the forced swimming test (FST) and exhibited a significant increase in oxidative-nitrosative stress markers, inflammatory mediators, including tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β), activation of the nuclear factor kappa B (NF-κB) signaling pathway and increased inducible nitric oxide synthase (iNOS) mRNA expression in the hippocampus, which was reversed by chronic treatment with icariin (20 or 40 mg/kg). Interestingly, icariin negatively regulated the activation of the nod-like receptor protein 3 (NLRP3) inflammasome/caspase-1/IL-1β axis in the hippocampus of CMS rats. These results confirm that icariin exerts antidepressant-like effects, which may be mediated, at least in part, by enhanced antioxidant status and anti-inflammatory effects on the brain tissue via the inhibition of NF-κB signaling activation and the NLRP3-inflammasome/caspase-1/IL-1β axis. Our findings provide new information to understand the antidepressant action of icariin, which is targeted to the NLRP3-inflammasom in brain.

RRM1 expression and clinical outcome of gemcitabine-containing chemotherapy for advanced non-small-cell lung cancer: A meta-analysis

BACKGROUND The predictive value of RRM1 to therapeutic efficacy of gemicitabine-containing chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) remains disputable. This meta-analysis is performed to systematically evaluate whether RRM1 expression is associated with the clinical outcome of gemcitabine-containing regimen in advanced NSCLC. METHODS An electronic search was conducted using the databases Pubmed, Medline, EMBASE, Cochrane library and CNKI, from inception to May, 2011. A systemic review of the studies on the association between RRM1 expression in advanced NSCLC and clinical outcome of gemcitabine-containing regimen was performed. Pooled odds ratios (OR) for the response rate, weighted median survival and time to progression were calculated using the software Revman 5.0. RESULTS The search strategy identified 18 eligible studies (n=1243). Response rate to gemcitabine-containing regimen was significantly higher in patients with low/negative RRM1 (OR=0.31, 95% CI 0.21-0.45, P<0.00001). NSCLC patients with low/negative RRM1 who were treated with gemicitabine-containing regimen survived 3.94 months longer (95% CI 2.15-5.73, P<0.0001) and had longer time to progression for 2.64 months (95% CI 0.39-4.89, P=0.02) than those with high/positive RRM1. CONCLUSIONS Low/negative RRM1 expression in advanced NSCLC was associated with higher response rate to gemcitabine-containing regimen and better prognosis. Large phase III randomized trials are required to identify whether RRM1 detection is clinically valuable for predicting the prognosis and sensitivity to gemcitabine-containing regimen in advanced NSCLC.

Association of pro-inflammatory cytokines, cortisol and depression in patients with chronic obstructive pulmonary disease.

Evidence suggests that pro-inflammatory cytokines and cortisol play a crucial role in the etiology of chronic obstructive pulmonary disease (COPD) and depression. Depression occurs commonly among COPD patients and an earlier diagnosis would be beneficial. This study investigated the associations between depression, sputum cytokines and salivary cortisol in COPD patients. The diurnal rhythms of sputum IL-1, IL-6, TNF-α and salivary cortisol were measured in COPD patients with depression compared to those only with depression, or COPD and healthy controls. The area under the diurnal variation curves (AUC) over the 24h time course and relative diurnal variation (VAR) were calculated while correlation and regression analysis were performed. Patients with co-morbid depression and COPD showed an increasing sputum IL-1, sputum TNF-α AUC and a decreasing salivary cortisol VAR (P<0.001). The combination of sputum TNF-α AUC, sputum IL-1 AUC, sputum IL-6 AUC and salivary cortisol VAR performed best as a potential biomarker in the diagnosis of depression in COPD patients, with a sensitivity of 94.74% and a specificity of 96.67%. Positive correlations were found between sputum IL-1 AUC and sputum TNF-α AUC versus depressive symptoms, respectively a negative correlation was found between salivary cortisol VAR and depression. They were independently associated with depression in logistic regression models. Depression in COPD is associated with higher 24-h overall levels of sputum IL-1, TNF-α and flattened diurnal salivary cortisol. These non-invasive sputum and salivary biomarkers may serve as a simple clinical tool for the early diagnosis of depression in COPD patients.

Sputum interleukin-6, tumor necrosis factor-α and Salivary cortisol as new biomarkers of depression in lung cancer patients☆

Depression is common among lung cancer patients. Increasing evidence has suggested that hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory cytokines may play a key role in the pathophysiology of depression as well as cancer. This pilot study investigated the efficacy of sputum interleukin (IL)-6, tumor necrosis factor (TNF)-α and salivary cortisol as new markers to support the diagnosis of depression in lung cancer patients. The diurnal rhythms of sputum IL-6, sputum TNF-α and salivary cortisol were measured in lung cancer patients with and without depression as well as depressed controls and healthy controls. The area under the diurnal variation curves (AUC) over the 24h time course and relative diurnal variation (VAR) were calculated. Receiver operating characteristic (ROC) analysis was performed. Patients with co-morbid depression and lung cancer showed highest level of sputum IL-6 AUC, sputum TNF-α AUC and lowest level of cortisol VAR (P<0.001). As a biomarker for depression, salivary cortisol VAR demonstrated an optimal cutoff point at 77.8% (AUC=0.94; 95% CI, 0.85-0.98), which is associated with a sensitivity of 82.1% and a specificity of 96.0%. Sputum IL-6 AUC demonstrated a sensitivity of 74.4% and a specificity of 92.0% (AUC=0.81; 95% CI, 0.69-0.90). These findings suggested that higher 24h overall levels of sputum IL-6, TNF-α and flattened diurnal salivary cortisol slopes were associated with depression in lung cancer patients. Sputum IL-6 AUC and salivary cortisol VAR performed best as biomarkers in the diagnosis of depression in lung cancer patients.

Airway Inflammation and Hypothalamic-Pituitary-Adrenal Axis Activity in Asthmatic Adults with Depression

Objective. To investigate the features of airway inflammation and hypothalamic-pituitary-adrenal axis (HPAA) activity in patients with asthma accompanied by depression. Methods. Adult asthmatics were recruited and enrolled into one of the two groups based on scores on the Hamilton Depression Rating Scale (HAMD): asthmatics with depression (HAMD score ≥8, n = 23), and asthmatics without depression (HAMD score <8, n = 41). In addition, 27 healthy individuals and 21 adults with depression only were enrolled as controls. Induced sputum and blood samples were collected for measurement of cytokines and other inflammatory factors. The diurnal rhythm profiles of salivary cortisol and other hormones were obtained for assessment of the HPAA activity. Results. For the group of asthmatics with depression, the mean HAMD score was 19.0, and for the group of asthmatics without depression, the HAMD score averaged 4.9(p < .001). Serum and sputum tumor necrosis factor alpha (TNF-α) were significantly higher in asthmatics with depression than those in the other groups (p < .05) while serum interferon-gamma (IFN-γ) was lower in asthmatics with depression than that in the other groups (p < .05). Twenty-four-hour urinary cortisol, salivary cortisol at 8 a.m. and 4 p.m. were lower in asthmatics with depression compared to other groups (p < .05). Conclusions. As compared to healthy individuals and those with asthma or depression alone, individuals with comorbid depression and asthma showed the highest level of pro-inflammatory cytokines and the lowest level of anti-inflammatory cytokines and cortisol. These observations may serve as a valuable reference for diagnosis and clinic therapies of depression in asthmatics.

Establishment and Comparison of Combining Disease and Syndrome Model of Asthma with “Kidney Yang Deficiency” and “Abnormal Savda”

The study was the first time to establish and compare two rat models of two common syndromes: Kidney Yang Deficiency syndrome (KYDS) in traditional Chinese medicine (TCM) and abnormal savda syndrome (ASS) in traditional Uighur medicine (TUM). Then, we also established and evaluated rat models of combining disease and syndrome models of asthma with KYDS or ASS. Results showed that usage of the high dose of corticosterone (CORT) injection or external factors could successfully establish the KYDS or ASS rat models, and the two models had similar changes in biological characterization, abnormal behaviors, dysfunction of hypothalamic-pituitary-target organ axes (HPTOA), and sympathetic/parasympathetic (S/P) nerve system but varied in different degrees. The rat models of combining disease and syndrome of asthma with KYDS or ASS had either pathological characteristics of asthma such as airway hyperresponsiveness (AHR), airway inflammation, airway remodeling, which were more serious than allergy exposure alone, or the syndrome performance of Kidney Yang Deficiency in TCM and abnormal savda in TUM. These findings provide a biological rationale for further investigation of combining disease and syndrome model of asthma as an effective animal model for exploring asthma based on the theory of traditional medicine.

Effects of Two Chinese Herbal Formulae for the Treatment of Moderate to Severe Stable Chronic Obstructive Pulmonary Disease: A Multicenter, Double-Blind, Randomized Controlled Trial

Objective The study aims to evaluate the efficacy and safety of two Chinese herbal formulae for the treatment of stable COPD. Methods A multicenter, double-blind, double-dummy, and randomized controlled trial (RCT) was conducted. All groups were treated with additional conventional medicines. There were a 6-month treatment and a 12-month follow-up for 5 times. Primary outcomes included lung function test, exacerbation frequency, score of SGRQ. Second outcomes consisted of 6MWD, BODE index, psychological field score, inflammatory factors and cortisol. Results A total of 331 patients were randomly divided into two active treatment groups (Bushen Yiqi (BY) granule group, n = 109; Bushen Fangchuan (BF) tablet group, n = 109) and a placebo group (n = 113). Finally 262 patients completed the study. BY granule & BF tablet increased the values of VC, FEV1 (%) and FEV1/FVC (%), compared with placebo. BY granule improved PEF. Both treatments reduced acute exacerbation frequency (P = 0.067), BODE index and psychological field score, while improved 6MWD. In terms of descent rang of SGRQ score, both treatments increased (P = 0.01). Both treatments decreased inflammatory cytokines, such as IL-8, and IL-17(P = 0.0219). BY granule obviously descended IL-17(P<0.05), IL-1β (P = 0.05), IL-6, compared with placebo. They improved the level of IL-10 and cortisol. BY granule raised cortisol (P = 0.07) and decreased TNF-α. Both treatments slightly descended TGF-β1. In terms of safety, subject compliance and drug combination, there were no differences (P>0.05) among three groups. Conclusions BY granule and BF tablet were positively effective for the treatment of COPD, and the former performed better in general. Trial Registration Chinese Clinical Trial Register center ChiCTR-TRC-09000530

Prevention of gallstones by Lidan Granule: Insight into underlying mechanisms using a guinea pig model

The aim of the study was to examine the mechanism of action of Lidan Granule (LDG) for the prevention of gallstones using a guinea pig model. One hundred guinea pigs were divided into five groups randomly: control (standard diet and saline), model [lithogenic diet (LD) and saline], LDG-H (LD and 2 g/kg of LDG), LDG-L (LD and 1 g/kg of LDG), and ursodeoxycholic acid (UDCA) (LD and UDCA) as the positive control. At 6 weeks, the rate of gallstone formation and weight of the adrenal gland were recorded and serum levels of inflammatory cytokines were measured. Levels of corticotrophin-releasing hormone (CRH) in the hypothalamus, adrenocorticotropic hormone (ACTH) in the hypophysis, and serum cortisol were determined. Bile components were tested with colorimetry. At 6 weeks, the rate of gallstone formation was significantly decreased in the LDG-H (14.29%) and LDG-L (21.43%) groups compared to the model group (81.25%; P<0.01). LDG treatment decreased the serum levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α (P<0.01). LDG decreased bile cholesterol and increased bile acid and phospholipid levels in the bile (P<0.01). LDG treatment recovered the function of the hypothalamic-pituitary-adrenal (HPA) axis by increasing the expression of CRH (P<0.01) and ACTH (P<0.05). LDG made the bile less lithogenic, improved the function of the HPA axis, and regulated the expression of inflammatory cytokines for the prevention of cholelithiasis.

The Anti-Inflammatory Effects of Invigorating Kidney and Supplementing Qi Chinese Herbal Formulae in Asthma Patients

Background The theories of Shen-reinforcement and Qi-supplementation are important in asthma treatment based on traditional Chinese medicine theories. Early studies suggested that Invigorating Kidney and Supplementing Qi herbal formulae, Bu Shen Fang Chuan (BSFC) and Bu Shen Yi Qi (BSYQ), conveyed promising results in asthma treatment. However, the efficacy and safety of the formulae need to be further investigated by a randomized double-blind clinical trial. Methods 328 eligible patients were randomly sent to BSFC, BSYQ, and placebo group. The two formulae were received as add-on therapy. The primary endpoints were rate of asthma exacerbation and Hamilton Rating Scale for Depression (HAM-D) score. The secondary endpoints included HPA axis function and inflammatory cytokine production profile. All indexes were measured before and after treatment. Results The primary endpoints were not improved in both groups; however, the depression levels of subgroup patients with HAM-D score > 5 were improved in BSFC group. HPA axis functions and inflammatory cytokines level were also improved by two formulae. The incidences of adverse events were similar among groups. Conclusions The two formulae had multiple advantage effects on neuroendocrine-immune system. They are worth used as a replacement therapy in asthma. Trial Registration This trial is registered with clinical trial number ChiCTR-PRC-09000529.